(R,R')-4'-Methoxy-1-naphthylfenoterol (MNF) promotes growth inhibition and apoptosis of human HepG2 hepatocarcinoma cells via cannabinoid receptor (CBR) activation. The synthetic CB1R inverse agonist, AM251, has been shown to block the anti-mitogenic effect of MNF in these cells; however, AM251 is also an agonist of the recently deorphanized, lipid-sensing receptor, GPR55, whose upregulation contributes to carcinogenesis. Here, we investigated the role of MNF in GPR55 signaling in human HepG2 and PANC-1 cancer cell lines in culture by focusing first on internalization of the fluorescent ligand Tocrifluor 1117 (T1117). Initial results indicated that cell pretreatment with GPR55 agonists, including the atypical cannabinoid O-1602 and l-α-lysophosphatidylinositol, dose-dependently reduced the rate of cellular T1117 uptake, a process that was sensitive to MNF inhibition. GPR55 internalization and signaling mediated by O-1602 was blocked by MNF in GPR55-expressing HEK293 cells. Pretreatment of HepG2 and PANC-1 cells with MNF significantly abrogated the induction of ERK1/2 phosphorylation in response to AM251 and O-1602. Moreover, MNF exerted a coordinated negative regulation of AM251 and O-1602 inducible processes, including changes in cellular morphology and cell migration using scratch wound healing assay. This study shows for the first time that MNF impairs GPR55-mediated signaling and, therefore, may have therapeutic potential in the management of cancer.
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http://dx.doi.org/10.1016/j.bcp.2013.11.020 | DOI Listing |
Anim Cells Syst (Seoul)
December 2024
Department of Oral Biochemistry, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, Republic of Korea.
(), a periodontal pathogen, has been implicated in the impairment of anti-tumor responses in colorectal cancer (CRC). The tumor microenvironment in CRC involves tumor-associated macrophages (TAMs), which are pivotal in modulating tumor-associated immune responses. The polarization of TAMs towards an M2-like phenotype promotes CRC progression by suppressing the immune system.
View Article and Find Full Text PDFAnim Cells Syst (Seoul)
January 2025
Department of Biochemistry, College of Natural Sciences, Chungnam National University, Daejeon, Korea.
Interferon gamma (IFNγ) is well-known for its ability to stimulate immune cells in response to pathogen infections and cancer. To develop an effective cancer therapeutic vaccine, CT26 colon carcinoma cells were genetically modified to express IFNγ either as a secreted form (sIFNγ) or as a membrane-bound form. For the membrane-bound expression, IFNγ was fused with Fas (mbIFNγ/Fas), incorporating the extracellular cysteine-rich domains, transmembrane, and cytoplasmic domains of Fas.
View Article and Find Full Text PDFFront Ophthalmol (Lausanne)
December 2024
Department of Ophthalmology & Visual Sciences, School of Medicine, Washington University in St. Louis, St Louis, MO, United States.
Background: Giant cell arteritis (GCA) is the most common vasculitis in patients older than 50 years and is considered a "do not miss" diagnosis. However, it remains a diagnostic challenge given overlapping clinical syndromes such as non-arteritic anterior ischemic optic neuropathy (NAION) and poorly explored imaging findings.
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Mol Clin Oncol
February 2025
Department of Urology Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Disulfidptosis, which was recently identified, has shown promise as a potential cancer treatment. Nonetheless, the precise role of long non-coding RNAs (lncRNAs) in this phenomenon is currently unclear. To elucidate their significance in bladder cancer (BLCA), a signature of disulfidptosis-related lncRNAs (DRlncRNAs) was developed and their potential prognostic significance was explored.
View Article and Find Full Text PDFMol Clin Oncol
February 2025
Department of Biological Sciences, Tennessee State University, Nashville, TN 37209, USA.
Although peptide vaccines offer a novel venue for cancer immunotherapy, clinical success has been rather limited. Cell-penetrating peptides, due to their ability to translocate through the cell membrane, could be conjugated to the peptide vaccine to2 enhance therapeutic efficiency. The S4 transduction domain of the shaker-potassium channel was conjugated to mammaglobin-A (MamA) immunodominant epitope (MamA2.
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